<abstract xmlns="http://www.w3.org/1999/xhtml"> Background: How to deliver sufficient therapeutic genes into cancer cells while causing fewer side effects are major challenges in cancer gene therapies. Receptor mediated gene delivery enables specific delivering therapeutic genes into target cancer cells and increases the efficacy. Objectives: We developed a novel receptor mediated short interference RNA (siRNA) expression plasmid delivery system against ovarian carcinoma cells with improved biocompatibility in vitro. Methods: Follice stimulating hormone (FSH) peptide (β: 33-55) was grafted to polyethylenimine (PEI) via a bifunctional polyethylene glycol (PEG) and complexed with anti chemokine c-x-c motif ligand 1 (CXCL1) plasmid DNA (pDNA) to form FSH-PEG-PEI/pDNA polyplexes at various N/P ratios. The cytotocity, transfection efficiency, and CXCL1 silencing effect were evaluated respectively. Results: The FSH-PEG-PEI/pDNA polyplexes showed low cytotoxicity, high transfection efficiency, and specific CXCL1 gene silencing effect. The 2% FSH-PEG-PEI conjugate complexed with pDNA at N/P ratio of 25 has better physicochemical properties. The therapeutic siRNA expression plasmid uptake by follice stimulating hormone receptor (FSHR) expression ovarian carcinoma cells was through a receptor-mediated manner. Conclusion: The FSH-PEG-PEI conjugate can be used as a novel receptor mediated gene delivery system against ovarian carcinomas. This strategy could be extended to a wide range of targeted gene therapeutics against different cancers.</abstract>

Background: How to deliver sufficient therapeutic genes into cancer cells while causing fewer side effects are major challenges in cancer gene therapies. Receptor mediated gene delivery enables specific delivering therapeutic genes into target cancer cells and increases the efficacy. Objectives: We developed a novel receptor mediated short interference RNA (siRNA) expression plasmid delivery system against ovarian carcinoma cells with improved biocompatibility in vitro. Methods: Follice stimulating hormone (FSH) peptide (β: 33-55) was grafted to polyethylenimine (PEI) via a bifunctional polyethylene glycol (PEG) and complexed with anti chemokine c-x-c motif ligand 1 (CXCL1) plasmid DNA (pDNA) to form FSH-PEG-PEI/pDNA polyplexes at various N/P ratios. The cytotocity, transfection efficiency, and CXCL1 silencing effect were evaluated respectively. Results: The FSH-PEG-PEI/pDNA polyplexes showed low cytotoxicity, high transfection efficiency, and specific CXCL1 gene silencing effect. The 2% FSH-PEG-PEI conjugate complexed with pDNA at N/P ratio of 25 has better physicochemical properties. The therapeutic siRNA expression plasmid uptake by follice stimulating hormone receptor (FSHR) expression ovarian carcinoma cells was through a receptor-mediated manner. Conclusion: The FSH-PEG-PEI conjugate can be used as a novel receptor mediated gene delivery system against ovarian carcinomas. This strategy could be extended to a wide range of targeted gene therapeutics against different cancers.

Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro

Department of Obstetrics and Gynecology of Shanghai Medical School, Shanghai 200000,

Department of Pharmaceutics, School of Pharmacy, Shanghai 200000,

Obstetrics and Gynecology Hospital, Shanghai 200000,

Department of Obstetrics and Gynecology of Shanghai Medical School, Shanghai 200000, China

Obstetrics and Gynecology Hospital, Shanghai 200000, China

Institutes of Biomedical Sciences, Fudan University, Shanghai 200000, China

Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200000,

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Background: How to deliver sufficient therapeutic genes into cancer cells while causing fewer side effects are major challenges in cancer gene therapies....

Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro

Article Category: Original article

Online veröffentlicht: 04. Feb. 2017

Seitenbereich: 185 - 194

DOI: https://doi.org/10.5372/1905-7415.0602.045

Schlüsselwörter
Follice stimulating hormone peptide, follice stimulating hormone receptor, ovarian carcinoma, polyplexes, receptor mediated gene delivery, siRNA expression plasmid

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro

Article Category: Original article

Online veröffentlicht: 04. Feb. 2017

Seitenbereich: 185 - 194

DOI: https://doi.org/10.5372/1905-7415.0602.045

SchlüsselwörterFollice stimulating hormone peptide, follice stimulating hormone receptor, ovarian carcinoma, polyplexes, receptor mediated gene delivery, siRNA expression plasmid

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Schlüsselwörter
Follice stimulating hormone peptide, follice stimulating hormone receptor, ovarian carcinoma, polyplexes, receptor mediated gene delivery, siRNA expression plasmid